Novel systems biology experimental pipeline reveals matairesinol’s antimetastatic potential in prostate cancer - an integrated approach of network pharmacology, bioinformatics, and experimental validation

Sep 21, 2026

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Matairesinol (MAT), a plant lignan known for anticancer activity in hormone-sensitive cancers, is evaluated as a therapeutic candidate against metastatic prostate cancer (mPC), where evidence remains limited. An integrative workflow combines network pharmacology and GeneMANIA-based functional association with bioinformatics target discovery across mPC and MAT, then applies molecular docking, molecular dynamics simulations, and experimental validation. Shared targets include 11 hubs and metastasis-linked pathways (e.g., EMT, migration regulation, PI3K-Akt, MAPK), supporting MAT’s antimetastatic effects in PC3 cells, while emphasizing the need for broader in vitro confirmation.

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Briefings in Bioinformatics, 2024, 25(5), bbae466 [https://doi.org/10.1093/bib/bbae466](https://doi.org/10.1093/bib/bbae466) Problem Solving Protocol Novel systems biology experimental pipeline reveals matairesinol’s antimetastatic potential in prostate cancer: an integrated approach of network pharmacology, bioinformatics, and experimental validation Rama Rajadnya1 , Nidhi Sharma1 , Akanksha Mahajan1 , Amrita Ulhe1 , Rajesh Patil2 , Mahabaleshwar Hegde3 , Aniket Mali 1 , * 1 Cancer Biology, Interactive Research School for Health Affairs (IRSHA), Bharati Vidyapeeth (Deemed to be University), Pune-Satara Road, Dhankawadi, Pune, Maharashtra 411043, India 2 Department of Pharmaceutical Chemistry, Sinhgad Technical Education Society, Sinhgad College of Pharmacy, Vadgaon (BK), Off Sinhgad Road, Pune, Maharashtra 411041, India 3 Innovative Nutrition, Interactive Research School for Health Affairs (IRSHA), Bharati Vidyapeeth (Deemed to be University), Pune-Satara Road, Dhankawadi, Pune, Maharashtra 411043, India *Corresponding author. Cancer Biology, Interactive Research School for Health Affairs (IRSHA), Bharati Vidyapeeth (Deemed to be University), Pune-Satara Road, Dhankawadi, Pune, Maharashtra 411043, India. E-mail: [aniket.mali@bharatividyapeeth.edu](aniket.mali@bharatividyapeeth.edu) Rama Rajadnya, first author and Ph.D. student, Biotechnology, IRSHA, BVDU, Pune. Aniket Mali, corresponding author, Assoc. Prof and Head of the Department. Akanksha Mahajan, Amrita Ulhe, and Nidhi Sharma, Ph.D. students, IRSHA, BVDU, Pune. Mahabaleshwar Hegde, Prof. Innovative Nutrition-IRSHA. Rajesh Patil, Principal and Prof. (Pharmaceutical Chemistry), Sinhgad College of Pharmacy, Pune. Abstract Matairesinol (MAT), a plant lignan renowned for its anticancer properties in hormone-sensitive cancers like breast and prostate cancers, presents a promising yet underexplored avenue in the treatment of metastatic prostate cancer (mPC) . To elucidate its specific therapeutic targets and mechanisms, our study adopted an integrative approach, amalgamating network pharmacology (NP), bioinformatics, GeneMANIA-based functional association (GMFA), and experimental validation. By mining online databases, we identified 27 common targets of mPC and MAT, constructing a MAT-mPC protein–protein interaction network via STRING and pinpointing 11 hub targets such as EGFR, AKT1, ERBB2, MET, IGF1, CASP3, HSP90AA1, HIF1A, MMP2, HGF, and MMP9 with CytoHuba. Utilizing DAVID, Gene Ontology (GO) analysis highlighted metastasis-related processes such as epithelial–mesenchymal transition, positive regulation of cell migration, and key Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, including cancer, prostate cancer, PI3K-Akt, and MAPK signaling, while the web resources such as UALCAN and GEPIA2 affirmed the clinical significance of the top 11 hub targets in mPC patient survival analysis and gene expression patterns. Our innovative GMFA enrichment method further enriched network pharmacology findings. Molecular docking analyses demonstrated substantial interactions between MAT and 11 hub targets. Simulation studies confirmed the stable interactions of MAT with selected targets. Experimental validation in PC3 cells, employing quantitative real-time reverse-transcription PCR and various cell-based assays, corroborated MAT’s antimetastatic effects on mPC. Thus, this exhaustive NP analysis, complemented by GMFA, molecular docking, molecular dynamics simulations, and experimental validations, underscores MAT’s multifaceted role in targeting mPC through diverse therapeutic avenues. Nevertheless, comprehensive in vitro validation is imperative to solidify these findings. Received: April 25, 2024. Revised: July 21, 2024. Accepted: September 5, 2024 © The Author(s) 2024. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ([https://creativecommons.or

FAQs

What integrative methods were used to study matairesinol’s role in metastatic prostate cancer?

The study used network pharmacology with GeneMANIA-based functional association, bioinformatics target and pathway enrichment, molecular docking, molecular dynamics simulations, and experimental validation in PC3 cells.

Which hub targets and pathways were highlighted in the analysis?

Eleven hub targets were identified, including EGFR, AKT1, ERBB2, and MET. Pathway enrichment emphasized metastasis-related processes and KEGG pathways such as cancer, prostate cancer, PI3K-Akt, and MAPK signaling.

How was the antimetastatic effect of matairesinol validated experimentally?

PC3 cell experiments were performed using quantitative real-time reverse-transcription PCR and multiple cell-based assays, confirming MAT’s antimetastatic effects in the mPC context.

Sep 21, 2026

Uploaded by Theodore